1. Field of the Invention
The present invention relates to an isolated protein increasing a cell infectivity of herpes simplex virus and use thereof.
This work has been supported in part by research grants from Korean Ministry of Education, Science & Technology [Project No.: M1053040003-08N3404-00310, Title: Cancer gene therapy by targeted HSV-1 development. And Project No.: M20702020001-08N0202-00110, Title: Development of combinational radiotherapeutic agents and validation system.]
2. Description of the Related Art
Herpes simplex virus (HSV) which is a DNA virus containing about 150 kb of genome is an enveloped icosahedral virion with a size of about 100 to about 200 nm. HSV enters a cell by attaching glycoprotein B (gB) or glycoprotein C (gC) of its envelope to glycosaminoglycan (GAG) of the surface of the cell, and binding glycoprotein D (gD) of its envelope to various receptors of the surface of the cell to induce fusion of the HSV with membranes of the cell (Spear P G. Cell Microbiol. 2004; 6(5):401-410; Spear P G, Eisenberg R J, Cohen G H. Virology. 2000; 275(1):1-8).
Receptors of the cell surface for HSV include HveA/HVEM, HveC/nectin-1, and HveB/nectin-2 proteins. Herpes virus entry mediator A (HveA/HVEM) is a member of a tumor necrosis factor receptor (TNFR) superfamily and acts as a receptor for HSV-1 and HSV-2 (Whitbeck J C et al., J. Virol. 1997; 71(8): 6083-6093). HveA/HVEM is often expressed in lymphoid tissues such as B-lymphoma or T-lymphoma (Montgomery R I et al., Cell. 1996; 87(3): 427-436). HveA/HVEM is composed of 4 cysteine-rich domains (CRDs).
Gene therapy includes introduction of foreign genes into individuals for the prevention and treatment of diseases. Vectors used for the introduction of the foreign genes include viral vectors or virus-derived vectors. Virus-derived vectors include an adenoviral vector, a retroviral vector, and a herpes simplex viral vector. The adenoviral vector has high gene delivery efficiency and may deliver genes into both proliferating and nonproliferating cells. On the other hand, repeated use of the adenoviral vector may induce strong immunoreactivity, and the size of genes is limited when using the adenoviral vector. The herpes simplex viral vector may deliver relatively large genes and also deliver genes into neural cells.
According to Laquerre S et al., erythropoietin is fused to N-terminal of glycoprotein C of herpes simplex viral surface to obtain erythropoietin-glycoprotein C fusion protein, and HSV containing the erythropoietin-glycoprotein C fusion protein is introduced into cells in which an erythropoietin receptor is expressed. However, since the virus is introduced into cells by an endocytosis instead of by a fusion, the HSV is degradated in the cells, and thus transduction efficiency of the HSV is low. (Laquerre S et al., J. Virol. 1998. December; 72(12): 9683-9697).